BACKGROUND: Limited evidence exists to support the simultaneous initiation of sodium-glucose cotransporter-2 inhibitors and finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in persons with chronic kidney disease and type 2 diabetes.
METHODS: We randomly assigned participants with chronic kidney disease (estimated glomerular filtration rate [eGFR], 30 to 90 ml per minute per 1.73 m2 of body-surface area), albuminuria (a urinary albumin-to-creatinine ratio of 100 to =5000 [with albumin measured in milligrams and creatinine measured in grams]), and type 2 diabetes, who were already taking a renin-angiotensin system inhibitor, in a 1:1:1 ratio to receive finerenone (with empagliflozin-matching placebo) at a dose of 10 or 20 mg per day, empagliflozin at a dose of 10 mg per day (with finerenone-matching placebo), or a combination of finerenone and empagliflozin. The primary outcome was the relative change in the log-transformed mean urinary albumin-to-creatinine ratio from baseline to 180 days. Safety was assessed.
RESULTS: At baseline, the urinary albumin-to-creatinine ratio was similar among the participants in the three groups; the median value was 579 (interquartile range, 292 to 1092) among those with available data (265 in the combination-therapy group, 258 in the finerenone group, and 261 participants in the empagliflozin group). At day 180, the reduction in the urinary albumin-to-creatinine ratio with combination therapy was 29% greater than that with finerenone alone (least-squares mean ratio of the difference in the change from baseline, 0.71; 95% confidence interval [CI], 0.61 to 0.82; P<0.001) and 32% greater than that with empagliflozin alone (least-squares mean ratio of the difference in the change from baseline, 0.68; 95% CI, 0.59 to 0.79; P<0.001). Neither agent, alone or in combination, led to unexpected adverse events. Symptomatic hypotension, acute kidney injury, and hyperkalemia leading to drug discontinuation were uncommon.
CONCLUSIONS: Among persons with both chronic kidney disease and type 2 diabetes, initial therapy with finerenone plus empagliflozin led to a greater reduction in the urinary albumin-to-creatinine ratio than either treatment alone. (Funded by Bayer; CONFIDENCE ClinicalTrials.gov number, NCT05254002.).
| Discipline Area | Score |
|---|---|
| Internal Medicine |  |
| Endocrine | |
| Nephrology | |
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
The short duration of the study as well as using a surrogate marker for progression of CKD make it extremely difficult to draw useful conclusions applicable in a clinical setting. Additionally, there was very limited analysis or discussion on the relative declines of eGFR between the groups.
This is a good start but following the effect on GFR would be more meaningful.
The value hinges on the prognostic validity of albumin-to-creatinine ratio.
As a hospitalist managing patients with chronic kidney disease and type 2 diabetes, I find this study highly relevant and timely. It offers compelling evidence supporting the simultaneous initiation of finerenone and empagliflozin — an approach not widely adopted in current practice. The demonstrated additive reduction in albuminuria with a manageable safety profile could influence prescribing decisions and promote earlier combination therapy in high-risk patients. The trial also highlights practical monitoring considerations (e.g., potassium and eGFR), making it directly applicable to inpatient and discharge planning workflows.